Antidepressants Found Unrelated to Suicide Risk

Action Points

Explain to patients that the purported association between antidepressants and increased suicide risk is a matter of ongoing scientific debate.

Inform patients that the current study found risk of suicide was decreased, not increased, with antidepressant use.

SEATTLE, Jan. 3 - Despite government-mandated warnings, antidepressants are not associated with an increase in the risk of suicide, according to a large population-based study.

The study of more than 65,000 children and adults treated for depression over a 10-year period starting in 1992 found that suicide risk declines, not rises, once a patient begins taking antidepressants, said Gregory E. Simon, M.D., M.P.H., a psychiatrist with the Group Health Cooperative, a non-profit health care organization here.

The observational study of patients enrolled in the Group Health Cooperative concluded that suicide risk is highest in the month before patients start medication, falls by more than one-half in the month after starting medication, and declines progressively after that, according to results published in the January issue of the American Journal of Psychiatry.

The journal is published by the American Psychiatric Association, which has been critical of FDA warnings about possible increased risk of suicide in children and adolescents brought on by treatment with newer antidepressants.

The FDA continues to stand by its warnings but will include the study in its comprehensive review of safety data of antidepressants in adults, said Paul Seligman, M.D., director of the FDA office responsible for post-marketing drug surveillance.

The FDA warnings, issued in October of 2004, were based on analysis of 24 pediatric trials of various antidepressants involving more than 4,400 patients. The analysis showed a greater risk of suicidal thinking and behavior during the first few months of treatment in those receiving antidepressants (4%) compared with placebo (2%). No actual suicides occurred.

A key difference between the FDA analysis and the current study is that the FDA analysis did not compare the risk of suicide before treatment to the risk following treatment and so may have missed the bigger picture, Dr. Simon and colleagues said. The current study looked at suicide risk from three months before treatment through six months after treatment.

In the month before patients went on medication, when suicide risk was highest, the rate of suicide attempts was nearly 100 per 100,000 treatment episodes, the authors said. This fell to fewer than 50 attempts per 100,000 during the first month of treatment and continued to decline in subsequent months. This pattern likely reflects depressive symptoms reaching a critical point that prompted therapy and improving thereafter,

Among patients treated with newer antidepressants, suicide risk during the first month of treatment was not significantly higher than during the subsequent five months (odds ratio=1.6; 95% confidence interval=0.9-3.1).

Among those treated with older drugs, risk was significantly higher during the first month of treatment compared with the subsequent five months (OR=3.6, 95% CI=1.8-6.9), most likely because these drugs simply take longer to work and not because they increase suicide risk, the study authors said.

Since the FDA warnings were announced, the APA has expressed concern that they might cause patients to forgo much-needed treatment with antidepressants because of exaggerated fears about suicide risk. In September, the association said that prescribing rates for antidepressants have declined by 20% for patients 18 and younger since the warnings were issued.

The current study "challenges the FDA warning that suicidal behavior may emerge after treatment is begun with antidepressant medications," an APA statement said.

The FDA's Dr. Seligman said the new study "reaffirms that the risks are generally small" and gives a more complete picture than a clinical trial, because suicidal patients are often excluded from clinical trials.

However, pending its comprehensive review of clinical trial safety data in adults, which will take at least a year, the FDA still urges physicians to carefully monitor patients being treated with antidepressants for worsening of symptoms or increased suicidal thinking and behavior, Dr. Seligman said.

Dr. Simon agreed with the FDA's recommendation that doctors carefully monitor patients taking antidepressants. "Keeping a close watch on patients after they begin taking these drugs is a good idea-although not because these medicines are especially risky or dangerous," he said.

"Patients need to be monitored to ensure they're getting the right medication in the amount that can help them feel better," he advised.

"There may be subgroups of people who become more agitated or suicidal after taking these drugs, and those people should seek help from a doctor or therapist right away if that happens," Dr. Simon said. "But our study showed that on average, the risk of suicide actually goes down after people start taking the antidepressant."

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